Lactobacillus Helveticus R0052 Alleviates Liver Injury By Modulating Gut Microbiome And Metabolome In D-galactosamine-treated Rats

Objective:The liver is an important digestive gland,and acute liver failure results in high mortality.Probiotics are considered potential adjuvant therapies for liver disease.This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052on acute liver injury and the underlying mechanisms.Methods:Sprague-Dawley rats were randomly divided into three experimental groups named the normal control(NC)group,positive control(PC)group and L.helveticus R0052-pretreated(R0052)group.Each group contained 8 rats.In the first seven days,the R0052 group was gavaged daily with 1 m L of freshly prepared L.helveticus R0052suspensions(3×10~9 CFU/ml).Meanwhile,the NC group and the PC group were gavaged with 1 m L of normal saline as a placebo.On the eighth day,D-Gal N was intraperitoneally injected into rats in the PC group and the R0052 group at a dose of 1.1 g/kg body weight to establish the acute liver injury model,while the rats in the NC group received the same dose of normal saline by intraperitoneal injection.After 24 hours,samples(blood,liver,ileum,faeces)were collected and assessed for histological injury,inflammation,intestinal barrier,gut microbiome and metabolome.Results:L.helveticus R0052 alleviated aminotransferase,bilirubin and total bile acid elevation and histological hepatic injuries.Additionally,L.helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors,tumour necrosis factor-?and nuclear factor-?b transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations.Additionally,L.helveticus R0052ameliorated intestinal abnormalities and regulated Toll-like receptors,claudin2 and mucin3 gene transcription in the intestine.These effects were associated with gut microbiome and metabolome modulation by L.helveticus R0052.Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome.Meanwhile,L.helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels.Conclusions:Our study demonstrated that L.helveticus R0052 alleviated D-Gal N-induced liver injury in rats by suppressing hepatic inflammation,enhancing the intestinal barrier,modulating the gut microbiome and regulating metabolome.These results indicate that L.helveticus R0052 is promising for alleviating ALF and provide new insights regarding the correlations among the microbiome,the metabolome,the intestinal barrier and liver disease.L.helveticus R0052 is a potential strain for liver disease and its effect on human patients need to be proved in future clinical trial.